@article{580a2ee4581b4ff2af98c3363d3d391b,
title = "Exosomal transfer of osteoclast-derived miRNAs to chondrocytes contributes to osteoarthritis progression",
abstract = "Osteoarthritis (OA) is a prevalent aging-related joint disease lacking disease-modifying therapies. Here, we identified an upregulation of circulating exosomal osteoclast (OC)-derived microRNAs (OC-miRNAs) during the progression of surgery-induced OA in mice. We found that reducing OC-miRNAs by Cre-mediated excision of the key miRNA-processing enzyme Dicer or blocking the secretion of OC-originated exosomes by short interfering RNA-mediated silencing of Rab27a substantially delayed the progression of surgery-induced OA in mice. Mechanistically, the exosomal transfer of OC-miRNAs to chondrocytes reduced the resistance of cartilage to matrix degeneration, osteochondral angiogenesis and sensory innervation during OA progression by suppressing tissue inhibitor of metalloproteinase-2 (TIMP-2) and TIMP-3. Furthermore, systemic administration of a new OC-targeted exosome inhibitor (OCExoInhib) blunted the progression of surgery-induced OA in mice. We suggest that targeting the exosomal transfer of OC-miRNAs to chondrocytes represents a potential therapeutic avenue to tackle OA progression.",
author = "Jin Liu and Xiaohao Wu and Jun Lu and Guangxin Huang and Lei Dang and Huarui Zhang and Chuanxin Zhong and Zongkang Zhang and Dijie Li and Fangfei Li and Chao Liang and Yuanyuan Yu and Zhang, {Bao Ting} and Lin Chen and Aiping Lu and Ge Zhang",
note = "Funding information: We thank technical staff (Y. S. Cheung, W. K. Chan, S. Lee and C. L. Chan) from Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, Hong Kong Baptist University for providing technical support on micro-CT, confocal imaging and flow cytometry analysis. We thank Guangzhou Biogene Biotechnology Co., Ltd. for providing technical support on mouse genotyping and AAV packaging. This work was supported by the funds from National Key R&D Program of China (2018YFA0800804 to L.C.) and National Natural Science Foundation Council of China (81702189 to J. Liu; 81803374 to J. Lu., 81802187 to G.H., 81703049 to F.L. and 81700780 to C.L.), the Theme-based Research Scheme from the Research Grants Council of Hong Kong (T12-201/20-R to A.L.), the General Research Funds from the Research Grants Council of Hong Kong (12102914 to G.Z., 12101117 to G.Z., 12136616 and 12103519 to J. Liu, 12101018 to F.L., 12102120 to Y.Y., 12102518 and 12100719 to A.L. and 14112915 to B.-T.Z.), the Basic and Applied Basic Research Fund from Department of Science and Technology of Guangdong Province (2019B1515120089 to G.Z.), the Natural Science Fund of Guangdong Province (2018030310355 to G.H.), the Shenzhen Science and Technology innovation fund (JCYJ20180302174121208 to J. Lu.), the Interdisciplinary Research Clusters Matching Scheme of Hong Kong Baptist University (RC-IRCs/17-18/02 to G.Z.; RC-IRCs/17-18/04 and RC-IRMS/15-16/01 to A.L.), the Inter-institutional Collaborative Research Scheme from Hong Kong Baptist University (RC-ICRS/19-20/01 to A.L.) Publisher copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc. ",
year = "2021",
month = apr,
day = "15",
doi = "10.1038/s43587-021-00050-6",
language = "English",
volume = "1",
pages = "368–384",
journal = "Nature Aging",
issn = "2662-8465",
publisher = "Springer",
number = "4",
}